Objective: This study aimed to assess perinatal morbidity, mortality rates, and neurodevelopmental outcomes in the management of fetal growth restriction (FGR) at a single tertiary institute. Methods: Among 2465 deliv...Objective: This study aimed to assess perinatal morbidity, mortality rates, and neurodevelopmental outcomes in the management of fetal growth restriction (FGR) at a single tertiary institute. Methods: Among 2465 deliveries between 2013 and 2019, 109 cases of FGR were reviewed retrospectively for causes, indications for pregnancy termination, perinatal death, overall neonatal outcomes, and long-term prognosis. Results: Excluding FGR due to congenital anomalies (n = 17), the mortality rate was 3.3% (3/92). One neonate delivered at 23 weeks developed cerebral palsy (1.1%). Retinopathy of prematurity occurred in four neonates (4.3%). Neurodevelopmental disorders were present in six neonates (6.5%), all of whom were delivered at 32 - 38 weeks. Significantly lower gestational age at delivery, lower birth weight, and higher umbilical artery resistance indices were observed in neonates with neurodevelopmental disorders. Conclusions: Intact survival before 27 weeks of gestation at delivery with FGR is uncommon. Neurodevelopmental disorders may still develop after delivery at 32 - 38 weeks;consideration should be given to the timing of delivery usingfetal ductus venosus Doppler waveforms measurements to reduce neurodevelopmental disorders.展开更多
Objective:Metabolic disturbances in the folate cycle in mothers can lead to fetal growth retardation(FGR).This study was to analyze the role of intergenic interactions among maternal folate cycle genes in the developm...Objective:Metabolic disturbances in the folate cycle in mothers can lead to fetal growth retardation(FGR).This study was to analyze the role of intergenic interactions among maternal folate cycle genes in the development of FGR.Methods:This case-control study recruited 365 women in the third trimester of pregnancy,including 122 FGR patients and 243 controls.The women were genotyped for 5 polymorphisms of the 4 folate cycle genes:MTR(rs1805087),MTRR(rs1801394),serine hydroxymethyl transferase(SHMT1;rs1979277),and TYMS(rs699517 and rs2790).The SNP×SNP interactions in the two-,three-,and four-locus models were analyzed using the multifactor dimensionality reduction method and a modification of it(the model-based multifactor dimensionality reduction method).Results:Four loci of maternal folate cycle genes(rs1805087 MTR,rs2790 TYMS,rs1801394 MTRR,and rs1979277 SHMT1)were associated with FGR in 3 significant models of single nucleotide polymorphism(SNP)×SNP interactions(two-,three-,and four-locus models)(P<0.05).The highest contribution to FGR was made by polymorphic loci rs1979277 SHMT1(1.70%of entropy),rs1805087 MTR(0.96%),and interactions between rs1979277 SHMT1×rs1805087 MTR(-1.11%)and rs1801394 MTRR×rs1979277 SHMT1(-0.64%).The four-locus maternal genotype combination AG rs1801394 MTRR×AA rs1805087 MTR×CT rs1979277 SHMT1×AG rs2790 TYMS was associated with an increased risk of FGR(β=2.69,P=0.012).FGR-associated SNPs were correlated with the expression of 16 genes(MTR,MTRR,SHMT1,ALKBH5,CTD-2303H24.2,ENOSF1,FAM106A,FOXO3B,LGALS9C,LLGL1,MIEF2,NOS2P2,RP11-806L2.6,SMCR8,TOP3A,and USP32P2)in various tissues and organs related to FGR pathophysiology.Conclusion:SNP×SNP interactions of maternal folate cycle genes(MTR,MTRR,SHMT1,and TYMS)are associated with the development of FGR.展开更多
Objective:To explore the levels of fibroblast growth factor 23(FGF23)during pregnancy and its relationship with intrauterine growth restriction(IUGR).Methods:Pregnant rats were classified into an ad libitum rat chow g...Objective:To explore the levels of fibroblast growth factor 23(FGF23)during pregnancy and its relationship with intrauterine growth restriction(IUGR).Methods:Pregnant rats were classified into an ad libitum rat chow group(ad libitum rat chow,AD group,n=25)and an undernutrition group(50%of their daily food requirement,UN group,n=25).The levels of maternal serum FGF23,tissue homogenate FGF23,and bone gla protein in fetal rats,and placental FGF23 mRNA and protein expression were examined by enzyme-linked immunosorbent assay,real-time qPCR analysis respectively.Finally,the effect of recombinant FGF23 on the viability of MG-63 cells was determined by cell proliferation assay.Data were analyzed with independent two-tailed t test and one-way analysis of variance.Spearman rank-order correlation coefficients(continuous variables)was performed to determine the relationship of results.Results:The diet restriction induced IUGR in rat offsprings,and the UN group exhibited a significantly lower FGF23 level(P<0.05,n=5).The FGF23 level was increased and peaked in maternal serum on gestation day(GD)15,but peaked in fetal and placenta on GD20.Moreover,the tissue homogenate levels of FGF23 and bone gla protein in fetal rats in both groups were positively correlated(r=0.923,P<0.05;r=0.925,P<0.05,respectively,n=15),FGF23 was localized to both decidual and labyrinth zones,with remarkably higher expression on GD20,P<0.05,n=5.In vitro,recombinant human FGF23 enhanced MG-63 cell viability,P<0.05,n=5.Conclusion:Prenatal undernutrition could decrease the FGF23 expression in fetal rats caused by the mother through the placenta,and induced the IUGR and hindered the ossification.And the FGF23 levels are peaked on GD15 mother but peaked on GD20 placenta and fetuses,these might be associated with the over compensation of maternal placenta on GD20.展开更多
Brain injury due to intrauterine growth restriction(IUGR) is a thorny clinical problem that often leads to permanent neurological deficits such as cerebral palsy.Few practical therapies can treat an IUGR-associated br...Brain injury due to intrauterine growth restriction(IUGR) is a thorny clinical problem that often leads to permanent neurological deficits such as cerebral palsy.Few practical therapies can treat an IUGR-associated brain injury.We employed acupuncture to treat a 6-month-old male patient with severe hypoxic-ischemic encephalopathy(HIE) due to IUGR,as confirmed by magnetic resonance imaging(MRI).Three courses of acupuncture treatment significantly improved some of the patient’s clinical characteristics,such as his insensitive responsiveness and motor deficits,with remarkably reversed HIE features on MRI at 1-year of age.This case suggests that acupuncture is a potential treatment option for an IUGRassociated brain injury and warrants further investigation.展开更多
Background:The presence of a single umbilical artery(SUA)is a fetal soft marker of congenital abnormalities.Among the most common related malformations,there are cardiological,nephrourological and digestive anomalies,...Background:The presence of a single umbilical artery(SUA)is a fetal soft marker of congenital abnormalities.Among the most common related malformations,there are cardiological,nephrourological and digestive anomalies,most of which are considered to have a vascular etiology.There is an association between increased incidence of intrauterine growth retardation and adverse perinatal indicators,but whether this association is due to related anomalies or isolated SUA(SUA)is controvisal.Methods:We reviewed 96 cases of iSUA and non-isolated SUA(niSUA),diagnosed in a period of two years in a referral hospital for high-risk pregnancies.Data on prenatal explorations,including fetal ultrasonography and karyotyping,were obtained.niSUA was diagnosed when no malformations were found prenatally or in postnatal evaluation.Results:Sixty-six newborns(68.8%)had no other anomalies and 30(31.3%)presented with a variety of malformations including heart diseases,urophaties,digestive,nervous and musculoskeletal disorders,genetic abnormalities and complex malformations.Cardiological and nephrourological abnormalities were found to be the most frequent association with a SUA(both in 23.8%of malformed SUA newborns).Intrauterine growth restriction was not higher in iSUA newborns than in a normal population.Utrasound allowed optimal prenatal diagnosis in most cases.Conclusions:The prognosis of the fetus with a SUA is determined by the presence of other malformations observed by an expert sonographer.If no other findings are made,only a routine physical examination should be performed in newborns,but no other complementary examinations are required.展开更多
Objective::This study aimed to determine:(1)whether recurrent deliveries of a small for gestational age(SGA)neonate are associated with increased obstetrical or neonatal complications;(2)whether the risk factors that ...Objective::This study aimed to determine:(1)whether recurrent deliveries of a small for gestational age(SGA)neonate are associated with increased obstetrical or neonatal complications;(2)whether the risk factors that can predict small for gestational age(SGA)recurrence.Methods::This study was based on Soroka Medical Center's Obstetrics electronic database.The database consisted of 109022 women who had 320932 deliveries between the year 1988-2014.The study cohort included 6.8%(7368/109022)of these patients who gave birth to a singleton SGA neonate on their first delivery and had more than one delivery.The study population was divided into two groups according to the outcome of the subsequent delivery:(1)women with sporadic SGA who delivered a non-SGA neonate(n=5416);(2)women with recurrent SGA(n=1952).SGA defined as birthweight<10 th percentile.Maternal and neonatal complications were compared between the two groups.Logistic regression was used to determine independent risk factors for SGA recurrence.Results::The prevalence of birthweight<5 th percentile was higher among the recurrent SGA group in the first delivery(P<0.001).Bedouin ethnicity was more prevalent in the recurrent SGA group(P<0.001).The rate of preterm delivery was higher in the first delivery of the recurrent SGA group(P=0.015).The sporadic SGA group had a higher rate of perinatal mortality during the first pregnancy(P=0.017).The rate of severe hypertension(P=0.005),polyhydramnios,meconium-stained amniotic fluid,nonreassuring fetal heart rate and total perinatal mortality(P<0.001)were higher in the second delivery of the recurrent SGA group.In a logistic regression model,preterm delivery and birthweight<5 th percentile at the first delivery was found to be independent risk factors for recurrence of an SGA neonate in the subsequent birth(relative risks:1.530,confidence interval:1.249-1.875;relative risks:1.826,confidence interval:1.641-2.030,respectively).Conclusion::Women with recurrent SGA neonates have specific clinical characteristics.Among women who deliver an SGA neonate,preterm delivery,and birthweight<5 th percentile are independent predictors for its recurrence.展开更多
文摘Objective: This study aimed to assess perinatal morbidity, mortality rates, and neurodevelopmental outcomes in the management of fetal growth restriction (FGR) at a single tertiary institute. Methods: Among 2465 deliveries between 2013 and 2019, 109 cases of FGR were reviewed retrospectively for causes, indications for pregnancy termination, perinatal death, overall neonatal outcomes, and long-term prognosis. Results: Excluding FGR due to congenital anomalies (n = 17), the mortality rate was 3.3% (3/92). One neonate delivered at 23 weeks developed cerebral palsy (1.1%). Retinopathy of prematurity occurred in four neonates (4.3%). Neurodevelopmental disorders were present in six neonates (6.5%), all of whom were delivered at 32 - 38 weeks. Significantly lower gestational age at delivery, lower birth weight, and higher umbilical artery resistance indices were observed in neonates with neurodevelopmental disorders. Conclusions: Intact survival before 27 weeks of gestation at delivery with FGR is uncommon. Neurodevelopmental disorders may still develop after delivery at 32 - 38 weeks;consideration should be given to the timing of delivery usingfetal ductus venosus Doppler waveforms measurements to reduce neurodevelopmental disorders.
基金President of the Russian Federation"Study of genetic factors of women's reproductive health"(MD-3284.2022.1.4)
文摘Objective:Metabolic disturbances in the folate cycle in mothers can lead to fetal growth retardation(FGR).This study was to analyze the role of intergenic interactions among maternal folate cycle genes in the development of FGR.Methods:This case-control study recruited 365 women in the third trimester of pregnancy,including 122 FGR patients and 243 controls.The women were genotyped for 5 polymorphisms of the 4 folate cycle genes:MTR(rs1805087),MTRR(rs1801394),serine hydroxymethyl transferase(SHMT1;rs1979277),and TYMS(rs699517 and rs2790).The SNP×SNP interactions in the two-,three-,and four-locus models were analyzed using the multifactor dimensionality reduction method and a modification of it(the model-based multifactor dimensionality reduction method).Results:Four loci of maternal folate cycle genes(rs1805087 MTR,rs2790 TYMS,rs1801394 MTRR,and rs1979277 SHMT1)were associated with FGR in 3 significant models of single nucleotide polymorphism(SNP)×SNP interactions(two-,three-,and four-locus models)(P<0.05).The highest contribution to FGR was made by polymorphic loci rs1979277 SHMT1(1.70%of entropy),rs1805087 MTR(0.96%),and interactions between rs1979277 SHMT1×rs1805087 MTR(-1.11%)and rs1801394 MTRR×rs1979277 SHMT1(-0.64%).The four-locus maternal genotype combination AG rs1801394 MTRR×AA rs1805087 MTR×CT rs1979277 SHMT1×AG rs2790 TYMS was associated with an increased risk of FGR(β=2.69,P=0.012).FGR-associated SNPs were correlated with the expression of 16 genes(MTR,MTRR,SHMT1,ALKBH5,CTD-2303H24.2,ENOSF1,FAM106A,FOXO3B,LGALS9C,LLGL1,MIEF2,NOS2P2,RP11-806L2.6,SMCR8,TOP3A,and USP32P2)in various tissues and organs related to FGR pathophysiology.Conclusion:SNP×SNP interactions of maternal folate cycle genes(MTR,MTRR,SHMT1,and TYMS)are associated with the development of FGR.
基金This work was supported by the National Natural Science Foundation of China(No.81571465,No.81871175)
文摘Objective:To explore the levels of fibroblast growth factor 23(FGF23)during pregnancy and its relationship with intrauterine growth restriction(IUGR).Methods:Pregnant rats were classified into an ad libitum rat chow group(ad libitum rat chow,AD group,n=25)and an undernutrition group(50%of their daily food requirement,UN group,n=25).The levels of maternal serum FGF23,tissue homogenate FGF23,and bone gla protein in fetal rats,and placental FGF23 mRNA and protein expression were examined by enzyme-linked immunosorbent assay,real-time qPCR analysis respectively.Finally,the effect of recombinant FGF23 on the viability of MG-63 cells was determined by cell proliferation assay.Data were analyzed with independent two-tailed t test and one-way analysis of variance.Spearman rank-order correlation coefficients(continuous variables)was performed to determine the relationship of results.Results:The diet restriction induced IUGR in rat offsprings,and the UN group exhibited a significantly lower FGF23 level(P<0.05,n=5).The FGF23 level was increased and peaked in maternal serum on gestation day(GD)15,but peaked in fetal and placenta on GD20.Moreover,the tissue homogenate levels of FGF23 and bone gla protein in fetal rats in both groups were positively correlated(r=0.923,P<0.05;r=0.925,P<0.05,respectively,n=15),FGF23 was localized to both decidual and labyrinth zones,with remarkably higher expression on GD20,P<0.05,n=5.In vitro,recombinant human FGF23 enhanced MG-63 cell viability,P<0.05,n=5.Conclusion:Prenatal undernutrition could decrease the FGF23 expression in fetal rats caused by the mother through the placenta,and induced the IUGR and hindered the ossification.And the FGF23 levels are peaked on GD15 mother but peaked on GD20 placenta and fetuses,these might be associated with the over compensation of maternal placenta on GD20.
基金Supported by National Natural Science Foundation of China:Mechanisms Studies of γ-frequency Auricular Electroacupuncture Facilitates APP/PS1 Mice Cognition via P2X7R/NLRP3/Caspase-1 Pathway(No.82104980)Beijing Municipal Administration of Hospitals Incubating Program:Mechanisms Studies of Auricular Electroacupuncture on Hypothalamic P2Y1R in the Regulating Body Weight of ob/ob Mice(No.PZ2022005)Youth Grant of Beijing Shijitan Hospital:Mechanisms Studies of Auricular Electroacupuncture on Hypothalamic P2Y1R in the Regulating Body Weight of db/db Mice(No.2021-q01)。
文摘Brain injury due to intrauterine growth restriction(IUGR) is a thorny clinical problem that often leads to permanent neurological deficits such as cerebral palsy.Few practical therapies can treat an IUGR-associated brain injury.We employed acupuncture to treat a 6-month-old male patient with severe hypoxic-ischemic encephalopathy(HIE) due to IUGR,as confirmed by magnetic resonance imaging(MRI).Three courses of acupuncture treatment significantly improved some of the patient’s clinical characteristics,such as his insensitive responsiveness and motor deficits,with remarkably reversed HIE features on MRI at 1-year of age.This case suggests that acupuncture is a potential treatment option for an IUGRassociated brain injury and warrants further investigation.
文摘Background:The presence of a single umbilical artery(SUA)is a fetal soft marker of congenital abnormalities.Among the most common related malformations,there are cardiological,nephrourological and digestive anomalies,most of which are considered to have a vascular etiology.There is an association between increased incidence of intrauterine growth retardation and adverse perinatal indicators,but whether this association is due to related anomalies or isolated SUA(SUA)is controvisal.Methods:We reviewed 96 cases of iSUA and non-isolated SUA(niSUA),diagnosed in a period of two years in a referral hospital for high-risk pregnancies.Data on prenatal explorations,including fetal ultrasonography and karyotyping,were obtained.niSUA was diagnosed when no malformations were found prenatally or in postnatal evaluation.Results:Sixty-six newborns(68.8%)had no other anomalies and 30(31.3%)presented with a variety of malformations including heart diseases,urophaties,digestive,nervous and musculoskeletal disorders,genetic abnormalities and complex malformations.Cardiological and nephrourological abnormalities were found to be the most frequent association with a SUA(both in 23.8%of malformed SUA newborns).Intrauterine growth restriction was not higher in iSUA newborns than in a normal population.Utrasound allowed optimal prenatal diagnosis in most cases.Conclusions:The prognosis of the fetus with a SUA is determined by the presence of other malformations observed by an expert sonographer.If no other findings are made,only a routine physical examination should be performed in newborns,but no other complementary examinations are required.
文摘Objective::This study aimed to determine:(1)whether recurrent deliveries of a small for gestational age(SGA)neonate are associated with increased obstetrical or neonatal complications;(2)whether the risk factors that can predict small for gestational age(SGA)recurrence.Methods::This study was based on Soroka Medical Center's Obstetrics electronic database.The database consisted of 109022 women who had 320932 deliveries between the year 1988-2014.The study cohort included 6.8%(7368/109022)of these patients who gave birth to a singleton SGA neonate on their first delivery and had more than one delivery.The study population was divided into two groups according to the outcome of the subsequent delivery:(1)women with sporadic SGA who delivered a non-SGA neonate(n=5416);(2)women with recurrent SGA(n=1952).SGA defined as birthweight<10 th percentile.Maternal and neonatal complications were compared between the two groups.Logistic regression was used to determine independent risk factors for SGA recurrence.Results::The prevalence of birthweight<5 th percentile was higher among the recurrent SGA group in the first delivery(P<0.001).Bedouin ethnicity was more prevalent in the recurrent SGA group(P<0.001).The rate of preterm delivery was higher in the first delivery of the recurrent SGA group(P=0.015).The sporadic SGA group had a higher rate of perinatal mortality during the first pregnancy(P=0.017).The rate of severe hypertension(P=0.005),polyhydramnios,meconium-stained amniotic fluid,nonreassuring fetal heart rate and total perinatal mortality(P<0.001)were higher in the second delivery of the recurrent SGA group.In a logistic regression model,preterm delivery and birthweight<5 th percentile at the first delivery was found to be independent risk factors for recurrence of an SGA neonate in the subsequent birth(relative risks:1.530,confidence interval:1.249-1.875;relative risks:1.826,confidence interval:1.641-2.030,respectively).Conclusion::Women with recurrent SGA neonates have specific clinical characteristics.Among women who deliver an SGA neonate,preterm delivery,and birthweight<5 th percentile are independent predictors for its recurrence.
